title: Anti-apoptotic effect of clusterin on cisplatin-induced cell death of retinoblastoma cells.
abstract: Clusterin is a cytoprotective chaperone protein that is known to protect various retinal cells. It was also reported to be overexpressed in several types of malignant tumors, whose chemoresistance correlates with the expression of clusterin. Herein, we investigated the effect of clusterin on cisplatin-induced cell death of retinoblastoma cells. Firstly, evaluation of clusterin expression demonstrated that it was highly expressed in human retinoblastoma tissues and cell lines (SNUOT-Rb1 and Y79) particularly in the area between viable cells around vessels and necrotic zones in the relatively avascular area in human retinoblastoma tissues. Furthermore, the effects of cisplatin on retinoblastoma cells were evaluated. Cisplatin (1 µg/ml) significantly affected cell viability of SNUOT-Rb1 cells by inducing caspase-3-dependent apoptosis. Notably, the cell death due to cisplatin was prevented by 5 µg/ml of clusterin administered 4 h prior to cisplatin treatment by inhibiting cisplatin-induced apoptosis. Furthermore, overexpression of clusterin exerted its anti-apoptotic effect on cisplatin-induced apoptosis, and effectively prevented cisplatin-induced cell death. These data suggest that clusterin, found to be expressed in human retinoblastoma, may exert anti-apoptotic effects on cisplatin-induced apoptosis and prevent cell death. Therefore, clusterin can contribute to cisplatin resistance of retinoblastoma.
authors.affiliation: Fight against Angiogenesis-Related Blindness Laboratory, Clinical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Hyun Beom
authors.initials: HB
authors.lastname: Song
authors.forename: Hyoung-Oh
authors.initials: HO
authors.lastname: Jun
authors.forename: Jin Hyoung
authors.initials: JH
authors.lastname: Kim
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Yu
authors.forename: Kyu-Won
authors.initials: KW
authors.lastname: Kim
authors.forename: Bon Hong
authors.initials: BH
authors.lastname: Min
authors.forename: Jeong Hun
authors.initials: JH
authors.lastname: Kim
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000096:biosynthesis; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage*; D051152:Clusterin / Q000096:biosynthesis / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D012175:Retinoblastoma / Q000188:drug therapy*
chemical_list: D051152:Clusterin; D053148:Caspase 3; D002945:Cisplatin